The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability

Abstract

Two forms of post-transcriptional control direct differential expression of the Saccharomyces cerevisiae genes encoding the AP1-like transcription factors Yap1p and Yap2p. The mRNAs of these genes contain respectively one (YAP1 uORF) and two (YAP2 uORF1 and uORF2) upstream open reading frames. uORF-mediated modulation of post-termination events on the 5'-untranslated region (5'-UTR) directs differential control not only of translation but also of mRNA decay. Translational control is defined by two types of uORF function. The YAP1-type uORF allows scanning 40S subunits to proceed via leaky scanning and re-initiation to the major ORF, whereas the YAP2-type acts to block ribosomal scanning by promoting efficient termination. At the same time, the YAP2 uORFs define a new type of mRNA destabilizing element. Both post-termination ribosome scanning behaviour and mRNA decay are influenced by the coding sequence and mRNA context of the respective uORFs, including downstream elements. Our data indicate that release of post-termination ribosomes promotes largely upf-independent accelerated decay. It follows that translational termination on the 5'-UTR of a mature, non-aberrant yeast mRNA can trigger destabilization via a different pathway to that used to rid the cell of mRNAs containing premature stop codons. This route of control of non-aberrant mRNA decay influences the stress response in yeast. It is also potentially relevant to expression of the sizable number of eukaryotic mRNAs that are now recognized to contain uORFs.